JANUMET ? 50 / 500 MG ( SITAGLIPTIN + METFORMIN HYDROCHLORIDE ) 56 FILM-COATED TABLETS

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use

JANUMET safely and effectively. See full prescribing information

for JANUMET.

JANUMET?

(sitagliptin and metformin hydrochloride) tablets, for

oral use

Initial U.S. Approval: 2007

WARNING: LACTIC ACIDOSIS

See full prescribing information for complete boxed warning.

? Postmarketing cases of metformin-associated lactic acidosis

have resulted in death, hypothermia, hypotension, and

resistant bradyarrhythmias. Symptoms included malaise,

myalgias, respiratory distress, somnolence, and abdominal

pain. Laboratory abnormalities included elevated blood lactate

levels, anion gap acidosis, increased lactate/pyruvate ratio,

and metformin plasma levels generally >5 mcg/mL. (5.1)

? Risk factors include renal impairment, concomitant use of

certain drugs, age ?65 years old, radiological studies with

contrast, surgery and other procedures, hypoxic states,

excessive alcohol intake, and hepatic impairment. Steps to

reduce the risk of and manage metformin-associated lactic

acidosis in these high risk groups are provided in the Full

Prescribing Information. (5.1)

? If lactic acidosis is suspected, discontinue JANUMET and

institute general supportive measures in a?

-INDICATIONS AND USAGE—————————-

JANUMET is a combination of sitagliptin, a dipeptidyl peptidase-4

(DPP-4) inhibitor, and metformin hydrochloride (HCl), a biguanide,

indicated as an adjunct to diet and exercise to improve glycemic

control in adults with type 2 diabetes mellitus. (1)

Limitations of Use:

? JANUMET should not be used in patients with type 1 diabetes or for

the treatment of diabetic ketoacidosis. (1)

? JANUMET has not been studied in patients with a history of

pancreatitis. (1, 5.2)

———————– DOSAGE AND ADMINISTRATION————————

? Individualize the starting dose of JANUMET based on the patient?s

current regimen. (2.1)

? Adjust the dosing based on effectiveness and tolerability while not

exceeding the maximum recommended daily dose of 100 mg

sitagliptin and 2000 mg metformin. (2.1)

? Give twice daily with meals, with gradual dose escalation, to reduce

the gastrointestinal effects due to metformin. (2.1)

? Prior to initiation, assess renal function with estimated glomerular

filtration rate (eGFR) (2.2)

o Do not use in patients with eGFR below 30 mL/min/1.73 m

2

.

o JANUMET is not recommended in patients with eGFR between

30 and less than 45 mL/min/1.73 m

2

.

? JANUMET may need to be discontinued at time of, or prior to,

iodinated contrast imaging procedures. (2.3)

——————— DOSAGE FORMS AND STRENGTHS ———————

Tablets: 50 mg sitagliptin/500 mg metformin HCl and 50 mg

sitagliptin/1000 mg metformin HCl (3)

——————————-CONTRAINDICATIONS——————————-

? Severe renal impairment: (eGFR below 30 mL/min/1.73 m

2

) (4)

? Metabolic acidosis, including diabetic ketoacidosis. (4)

? History of a serious hypersensitivity reaction to JANUMET,

sitagliptin, or metformin, such as anaphylaxis or angioedema. (5.9,

6.2)

———————– WARNINGS AND PRECAUTIONS————————

? Lactic acidosis: See boxed warning. (5.1)

? There have been postmarketing reports of acute pancreatitis,

including fatal and non-fatal hemorrhagic or necrotizing pancreatitis.

If pancreatitis is suspected, promptly discontinue JANUMET. (5.2)

? Heart failure has been observed with two other members of the

DPP-4 inhibitor class. Consider risks and benefits of JANUMET in?

patients who have known risk factors for heart failure. Monitor

patients for signs and symptoms. (5.3)

? There have been postmarketing reports of acute renal failure,

sometimes requiring dialysis. Before initiating JANUMET and at

least annually thereafter, assess renal function. (5.4)

? Vitamin B12 deficiency: Metformin may lower vitamin B12 levels.

Measure hematologic parameters annually. (5.5)

? When used with an insulin secretagogue (e.g., sulfonylurea) or with

insulin, a lower dose of the insulin secretagogue or insulin may be

required to reduce the risk of hypoglycemia. (5.7)

? There have been postmarketing reports of serious allergic and

hypersensitivity reactions in patients treated with sitagliptin (one of

the components of JANUMET), such as anaphylaxis, angioedema,

and exfoliative skin conditions including Stevens-Johnson

syndrome. In such cases, promptly stop JANUMET, assess for

other potential causes, institute appropriate monitoring and

treatment, and initiate alternative treatment for diabetes. (5.9)

? Severe and disabling arthralgia has been reported in patients taking

DPP-4 inhibitors. Consider as a possible cause for severe joint pain

and discontinue drug if appropriate. (5.10)

? There have been postmarketing reports of bullous pemphigoid

requiring hospitalization in patients taking DPP-4 inhibitors. Tell

patients to report development of blisters or erosions. If bullous

pemphigoid is suspected, discontinue JANUMET. (5.11)

? There have been no clinical studies establishing conclusive

evidence of macrovascular risk reduction with JANUMET. (5.12)

—————————— ADVERSE REACTIONS ——————————

? The most common adverse reactions reported in ?5% of patients

simultaneously started on sitagliptin and metformin and more

commonly than in patients treated with placebo were diarrhea,

upper respiratory tract infection, and headache. (6.1)

? Adverse reactions reported in ?5% of patients treated with

sitagliptin in combination with sulfonylurea and metformin and more

commonly than in patients treated with placebo in combination with

sulfonylurea and metformin were hypoglycemia and headache. (6.1)

? Hypoglycemia was the only adverse reaction reported in ?5% of

patients treated with sitagliptin in combination with insulin and

metformin and more commonly than in patients treated with

placebo in combination with insulin and metformin. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Merck

Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., at 1-877-

888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

——————————-DRUG INTERACTIONS——————————-

? Carbonic anhydrase inhibitors may increase risk of lactic acidosis.

Consider more frequent monitoring. (7.1)

? Drugs that reduce metformin clearance (such as ranolazine,

vandetanib, dolutegravir, and cimetidine) may increase the

accumulation of metformin. Consider the benefits and risks of

concomitant use. (7.2)

? Alcohol can potentiate the effect of metformin on lactate

metabolism. Warn patients against excessive alcohol intake. (7.3)

———————– USE IN SPECIFIC POPULATIONS ———————–

? There are no adequate and well-controlled studies in pregnant

women. To report drug exposure during pregnancy call 1-800-986-

8999. (8.1)

? Geriatric Use: Assess renal function more frequently. (8.5)

? Hepatic Impairment: Avoid use in patients with hepatic impairment.

(8.7)

See 17 for PATIENT COUNSELING INFORMATION and Medication

Guide.

Revised: 8/2019